Click here to access the full paper, 'Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use', as published in the journal NanoImpact.

Stewart Bland: I’d like to start by asking if you can introduce yourself and your group and tell us about your background.

Philip Demokritou: Okay, I’m Phillip Demokritou from Harvard University, the School of Public Health and I’m the director of the Centre for Nanotechnology and Nanotoxicology and also, another centre, funded by NIHS, the Centre for Nanosafety Research. So, my research focuses primarily on both implications of nanotechnology but also applications. So, the centres I mention there are a platform that bring together the people working on developing, designing new materials, nanomaterials and nanotechnology applications. And also, we’re trying to understand the fundamental nano-bio interactions and the potential environmental health and safety implications of nanomaterials.

My background is very diverse. Obviously, I’m a public health expert. That’s why I’m a faculty of the School of Public Health and its other section of engineering and life health sciences. Focusing, primarily, on understanding the pathogenesis of environmental industrial diseases. I’m based in the Department of Environmental Health Sciences at the School of Public Health and our research focus is primarily associated with the understanding the pathogenesis of environmentally-induced diseases.

Stewart Bland: That’s fantastic. Thank you. So, in your study, published in NanoImpact, you reported on the toxilogical implications of nanomaterials used by laser printers. Before we discuss the study, can you tell us why there’s concern over the safety of nanomaterials?

Philip Demokritou: Sure. You know, nanomaterials are unique because anything in the nanoscale, any material in the nanoscale has unique properties, in general. And those are physio-chemical properties, mechanical properties and that’s what makes them really unique for so many applications in every field of science. Now, on the other hand, nanoscale is the scale of nature. So, we do know now, because nanotoxicology (or nanosafety) this has been around for 10 or 15 years. We do have, really, reasons to worry that some of these materials… they can really, because of their size and their unique properties, they can really bypass biological barriers and they can interact with cells and can translocate from the rudimentary and can really be problematic.

Stewart Bland: So, in your study, you looked at particles emitted by laser printers. Just what are these particles and why did you decide to look at these?

Philip Demokritou: Yes, you know the new industrial model, as I already mentioned, is the nano-debedder, or other products or other applications out there. You know, industries, scientists like myself, we’re trying to take advantage of the unique properties in the nanoscale and a lot of products in the market currently, they’re nano in nature. So, this project actually started as a student project in one of my classes.

We started looking at products that, potentially, switched to nano and we started looking into toners, printing equipment, and we discovered (it wasn’t a big surprise for me) that these products, they were nano-enabled products. The industry, in the toner formulation, incorporate a lot of nano-additives there (for a reason, of course, to increase printing quality). And also, the problem that the industry had was the ozone generation from printing equipment, which was due to this corona that was used there to release ions to charge these large toner particles, so they can go and stick on the paper and make the printing perfect. So, they got rid of the corona and they switched to these nano-additives and especially metal oxides that, we do know, that they come with charge, on their own. So, they start switching and adding these nano-additives in their toner formulations. And, of course, they didn’t really pay attention, obviously, to those nano-additives that would be released during printing, which, as we confirm in many earlier studies, that’s the case.

So, that’s how we ended up studying these printer-emitted particles, which is a very complex mixture. You have all these nano-additives emitted and, more importantly, you have other gaseous co-pollutants, because the chemical composition of these toners is primarily organics and you have other gaseous components are needed and that’s how these PEPs are formed.

Stewart Bland: So, can you take us through how you approached the study?

Philip Demokritou: Yes, this is a big challenge in nanotoxicology. Assessing the risk of nanomaterials is: how do we link the real-world exposures beyond the pristine materials? Pristine nanomaterials to what people like you and I, as consumers, were getting exposed. So, you have the nanomaterials that... Usually nanomaterials are added in the product, in this particular case, it’s toner formulation and that’s what makes it a nano-enabled product. And across the life-cycle of this product there is a potential, for instance, during the consumer use, during printing in this case, for these nano-additives there to be released.

So, linking and studying the life-cycle implications of a nano-enabled product somatologically is not trivial. And that’s what we really want to link – these real-world exposures and, in this particular case, during consumer use to toxicology and, of course, assessing the risk. In order to assess the risks, you need not only the tox data, you need also the exposure data and that’s something usually… This nano-toxicology field doesn’t pay full attention.

So, this is the methodological power of the study, that we are linking to real-world exposure. We’re studying the release dynamics of these nano-additives and we’re trying to understand their biological properties and potential health implications.

There are many ways that we are doing this. We can use different experimental models. We build a platform that enables us to study the release dynamics in the lab and also, we use extensively different experimental models and those can be cellular models, to assess the mechanistic pathways for these particles. We collect these particles, size-fractionate them and look at their chemical composition. That’s very important information, especially if you try to apportion certain chemicals for certain health outcomes, you need to know the details of the exposures. So we characterise extensively the physiochemical properties of these printer-emitted engineered nanoparticles and through these various experimental models which can be cellular models or animal models like the study we published in NanoImpact. We’re trying to understand the toxicological implications.

Stewart Bland: So, what did you find in the study and should we be concerned?

Philip Demokritou: As I mentioned earlier, we’ve been working in assessing the properties of these printer-emitted engineered nanoparticles and also understanding the biological potential of these nanoparticles. So, we publish not only… this is a series of studies. The NanoImpact one is one of the latest ones we published.

But, just to summarise what we know: These PEPs, these printer-emitted particles, we proved that they are bio-active and they can elicit an array of unfavourable biological responses, both at the cellular level, but also at the organism level. Our latest studies, just to mention a few of these responses, include significant changes in cell viability. Also, we discovered some hereditary genetic material changes. We also showed that they can generate reactive-ox species and inflammatory responses.

So, all these outcomes they really show us that we need to pay attention for potential deleterious effects when these particles are inhaled. Of course, we need to still study more extensively and understand the mechanistic aspects, so we still have a lot of work to do. But I think these preliminary data from this series of studies make the case that when you see these kind of changes in the cellular environment and also at the people level and we do know that, generally speaking, exposures to environmental stressors can really be linked to serious health problems down the line. We can extend beyond the respiratory, but you can include cardiovascular diseases and other points.

Most importantly, this kind of implication study, we hope, will start the conversation with regulators, of course, to establish new guidelines for the safe use and toxicological screening of nano-enabled products across the life-cycle. We also hope that we’ll encourage the printing manufacturers to integrate hardware corrective measures to eliminate the release of nano-additives during printing.

Finally, I truly believe that assessing nano risk early on, during the material product development, when there is still a window to apply several design approaches, we’ll maximise the benefits of using nanoscale materials, but also eliminate potential environmental health implications. This is the way towards a more sustainable nanotechnology industry. Our society cannot afford developing and introducing new materials and chemicals into the market and cleaning the mess 30 years later, as we have done in the past. I think we really need to work together: researchers, regulators and industry to develop, in a more sustainable way, nanotechnology and new materials.

Stewart Bland: So, what’s next for this project?

Philip Demokritou: We have a number of studies, currently. We’re looking for… we’re focusing primarily on cardiovascular end points. And, just to make the case here, exposures from printing equipment in general, beyond laser printers, are happening not only at the office environment, but at the occupational level. In the United States alone, there are close to 150,000 workers in the photocopying industry. So, this is a major occupational hazard in addition to potential exposures at the office, or even at the home, micro environment.

So, we try to understand the potential for cardiovascular effects. One of the things we learnt from ambient particle toxicology, especially for ultra-fine particles also particles more or less of the same size, emitted from, primarily from compression sources. We do know that they are linked and we have a lot of epidemiological data linking these kind of exposures to cardiovascular effects.

So, when you inhale these particles, because they are tiny, they go deep into the lungs and they can really be translocated and we discovered that they can cause, among others, not just respiratory diseases but also cardiovascular effects. So, we have a project that focuses on assessing potential cardiovascular effects of PEPs. We’re also about to start a human health study in Singapore. This is a collaboration we have with Nanyang Technological University in Singapore to establish an occupational cohort and we will monitor workers in the printing industry over a course of time and try to understand the pathogenesis of certain diseases. So, this is, pretty much, the research agenda here for us.

Stewart Bland: Excellent. Thank you. So, finally, as always, I’d like to finish by asking: In your opinion, what are the hot topics in material science right now?

Philip Demokritou: That’s an endless list. In a way, the material research and nano is powering. I mean, the sky is the limit. I can mention a few areas that we are working. I truly believe that material research and, of course, nanotechnology in general can help our society to address a number of major issues. From food safety, that’s an area for instance, that we have a number of ongoing projects. Our society pays a huge bill in terms of foodborne diseases and also food waste and that’s where material science and technology can really play a significant role, developing new antimicrobial platforms, or even optimise the delivery of agrichemicals, that’s an area that can really make… we can make a difference. And we need new tools dealing with these kind of problems, which have been around forever of course. But, for whatever reason, we haven’t invested, as a society, developing new technologies dealing with microbes. So that’s an area, definitely, that material science can play a significant role.

Of course, the most exciting stuff is happening in the interplay of biology and engineering and I can mention a few areas: theranostics and developing novel approaches for theranostics. I think that’s another area we will see research in, in the years ahead.

But again, the sky’s the limit, so we need new materials, for energy applications and I think this is an exciting area of research to be in right now.

Please introduce yourself, and tell us about your role and your background.

Tim Nunney:

My name’s Tim Nunney, and I’m a product manager within the Nanoscale Materials Analysis group for Thermo Fisher Scientific. I’m responsible for marketing the surface analysis products, the instruments that use x-ray photoelectron spectroscopy, and so my role really encompasses organizing demonstrations for customers, running our webinar program, generating collateral, going to trade shows – all those kind of things. I’ve worked for Thermo for ten years now, and had roles in operations, down on the factory floor as well as in the marketing group. My background in surface science really goes back almost twenty years, through a post-doctoral position at the University of Southampton, before I started here at Thermo. Before that, I did a PhD in surface science at the University of Liverpool.

Stewart Bland:

Fantastic. So Thermo Fisher have recently unveiled the Nanoscale Centre of Excellence. So, just what is the Nanoscale Centre of Excellence?

Tim Nunney:

The Centre is a refurbishment of the facilities that we have here at our factory in East Grinstead, in the south of England. We’ve been based in the town for almost fifty years now. We’ve actually been in the current building since the mid-Eighties, I think. What we’ve done is really brought it up to the state-of-the-art, so that it can fulfil the several requirements that we need from the lab. Firstly, it provides the perfect showcase for both our microanalysis and surface analysis products, key instruments for the analysis materials at the nanoscale. Customers typically want to spend several days really getting under the skin of the instruments and their capabilities, and the new lab really enhances that experience. It gives them the opportunity to see not only the instrument maybe that they came to see, but how our other technologies may be of benefit to them.
Secondly, the Centre will be used to host training events for our customers, to help people get the very best from their instruments and their data, and also to host the seminar events, a bit like the one that we held last week for the grand opening of the Centre, and again this allows us to engage with the community at large, and bring them into the facility to see how we can benefit their analysis.

The last thing the Centre provides is a venue where we can foster collaboration with groups around the world. We’re investigating current materials challenges, and developing the materials of the future. The lab provides the range of instrumentation, including new capabilities like the argon cluster ion beam profiling source, which our collaborative partners may not have easy access to. Having the new Centre also allows us to engage with the academic community in the UK, and allows us to collaborate on PhD and EngD studentships too.

Stewart Bland:

I see, thank you. So what are the plans for the future of the Centre? What’s the ultimate goal?

Tim Nunney:

The goal is to continue to both reflect and, as much as possible, anticipate the needs of researchers working in materials science. We want to deliver a facility that shows how Thermo Fisher Scientific can work with scientists to achieve their aims. At present, we have all our surface analysis instruments, as I’ve mentioned, and our triple system of microanalysis products for electron microscopes installed into the lab. In the future, we want to be able to expand that, to really be able to show how instruments from other relevant areas of the Thermo portfolio, for example Raman spectroscopy, can be brought to bear in the issues that our customers have. It’s rare these days that you can find a solution to a problem with just one experimental technique, perhaps despite our best efforts to say that to you, and so having a full range of state-of-the-art analysis equipment available in one location will allow us to further develop collaborations, leading to methods and strategies, that we hope can enable our customers to overcome the materials problems of the future.

Stewart Bland:

Fantastic, thank you. So nano covers a lot of materials and technologies. Will the Centre be focusing on any particular areas?

Tim Nunney:

Well, as you say, nano does cover an awful lot of ground, and our customers typically are looking at nanoscale problems across a very broad range of areas. Recently we’ve seen some nanoscale problems in areas such as art restoration, and the forensic analysis of fabric coatings, which are a little bit outside maybe the usual expectations of nanoscale materials. It goes without saying that, looking at graphene and other 2D materials, is something that we are very involved in, and looking at in particular chemical modification in ultra-thin layers is one of the key strengths of x-ray photoelectron spectroscopy. Our experience in working with more traditional semiconductor research has given us the tools in our software and in our instruments to be able to work in these new carbon-based areas too. What we are seeing is a focus on materials for energy generation as well, particularly for photovoltaic applications, and also in energy storage, with materials for producing lighter and thinner lithium ion-based batteries, for example. Biotechnology is another key growth area. We tend to be involved in looking at the development of materials like biosensors, perhaps created through molecular self-assembly, and also the analysis of biomimetic coatings for implant devices.

Stewart Bland:

So finally, I’d like to finish, as always, by asking, in your opinion, what are the hot topics in materials science right now?

Tim Nunney:

The areas of materials science, I think, that we’re really seeing as hot are across maybe three broad categories. One is the move away from looking at ultra-thin film oxides for semiconductors, and moving into polymer-based electronics, particularly in applications such as touchscreens, and of course the rise of functionalized carbon nanomaterials, as I mentioned in the previous answer. It’s something else that we’re seeing more and more of in that kind of area.

The other side of the need for energy efficiency, aside from the generation of storage materials, is looking at the materials used in the construction of vehicles, and the development of strong and light materials, making sure that they’re easy to combine as well, and looking how they can form these composite.

Another important area is catalysis, and in particular band-gap engineering, for example to allow photo-catalysts to work more efficiently in sunlight. Getting this right, at the right cost, would enable their use more widely in applications like water purification. I think it’s fair to say that a lot of the driving force we see in hot areas is in materials science at the moment is based around environmental issues, be it energy efficiency, better use and re-use of resources, or the development of new materials to replace those that will become increasingly difficult to source.

]]>Thu, 22 May 2014 10:30:00 GMThttps://www.materialstoday.com/nanomaterials/podcasts/the-nanoscale-centre-of-excellence/Targeted drug deliveryhttps://www.materialstoday.com/biomaterials/podcasts/targeted-drug-delivery/
This week Dr. Zhen Gu from North Carolina State University and the University of North Carolina at Chapel Hill spoke to Stewart Bland about targeted drug delivery.

Researchers have developed a technique for creating nanoparticles that carry two different cancer-killing drugs into the body and deliver those drugs to separate parts of the cancer cell where they will be most effective. Gu’s research team developed nanoparticles with an outer shell made of hyaluronic acid (HA) woven together with TRAIL. The HA interacts with receptors on cancer cell membranes, which “grab” the nanoparticle. Enzymes in the cancer cell environment break down the HA, releasing TRAIL onto the cell membrane and ultimately triggering cell death.